Arbuckle Rebecca B, Griffith Niesha L, Iacovelli Lew M, Johnson Philip E, Jorgenson James A, Kloth Dwight D, Lucarelli Charles D, Muller Raymond J
Department of Drug Use Policy and Pharmacoeconomics, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Pharmacotherapy. 2008 May;28(5 Pt 2):1S-15S. doi: 10.1592/phco.28.5supp.1S.
Erythropoiesis-stimulating agents (ESAs) are approved as an alternative to blood transfusions for treating anemia secondary to chemotherapy in patients with cancer. Recently, ESAs have been a source of controversy and confusion in the oncology community. This began when two European trials-the Breast Cancer Erythropoietin Survival Trial (BEST) and the Advanced Head-and-Neck Cancer Treated with Radiotherapy (ENHANCE) Study-raised safety concerns about decreased overall survival and increased venous thromboembolic events. In 2004, the United States Food and Drug Administration (FDA) convened its Oncologic Drugs Advisory Committee (ODAC) to review the data and reassess the risks and benefits of ESAs in patients with cancer. On May 10, 2007, ODAC reconvened when five trials (BEST, ENHANCE, AMG-20010103, AMG-20000161, and EPO-CAN-20) showed decreased overall survival. The briefing document noted that studies demonstrating detrimental effects on survival and/or tumor outcomes used an unapproved treatment regimen designed to maintain hemoglobin levels above 12 g/dl. On May 14, 2007, just days after the ODAC reconvened, the Centers for Medicare and Medicaid Services (CMS) released a proposed decision memo for a national coverage determination (NCD) imposing restrictions on ESAs. For health care providers, aspects of the proposed NCD were markedly inconsistent with FDA-approved ESA use and generally were considered ambiguous and unclear. Over objections of several professional associations and members of Congress, on July 30, 2007, CMS posted the final NCD and declared it effective immediately. When compared with FDA-approved labeling and professional society guidelines, the NCD revealed differences in ESA initiation, dosage escalation, dosage reduction, and definition of response. These discrepancies have generated confusion among health care providers, who are struggling over whether they can feasibly provide a dual system of care-one for Medicare patients and another for non-Medicare patients-that is evidence based. With this supplement, we hope to educate health care providers on the issues and challenges associated with policy-guided health care when discrepancies exist between the policy and evidence-based practice; offer guidance on implementing the NCD; and highlight the important role of pharmacists in the process.
促红细胞生成素（ESAs）被批准作为癌症患者化疗继发贫血时输血的替代疗法。最近，ESAs在肿瘤学界引发了争议和困惑。这始于两项欧洲试验——乳腺癌促红细胞生成素生存试验（BEST）和放疗治疗晚期头颈癌（ENHANCE）研究——引发了对总体生存率降低和静脉血栓栓塞事件增加的安全担忧。2004年，美国食品药品监督管理局（FDA）召集其肿瘤药物咨询委员会（ODAC）审查数据，并重新评估ESAs对癌症患者的风险和益处。2007年5月10日，当五项试验（BEST、ENHANCE、AMG - 20010103、AMG - 20000161和EPO - CAN - 20）显示总体生存率降低时，ODAC再次召开会议。简报文件指出，显示对生存和/或肿瘤结局有不利影响的研究使用了未经批准的治疗方案，旨在将血红蛋白水平维持在12 g/dl以上。2007年5月14日，就在ODAC再次召开会议几天后，医疗保险和医疗补助服务中心（CMS）发布了一份关于全国医保覆盖范围确定（NCD）的拟议决策备忘录，对ESAs施加限制。对于医疗保健提供者来说，拟议的NCD的一些方面与FDA批准的ESAs使用明显不一致，并且通常被认为含糊不清。不顾几个专业协会和国会议员的反对，2007年7月30日，CMS公布了最终的NCD并宣布立即生效。与FDA批准的标签和专业协会指南相比，NCD在ESAs的起始、剂量递增、剂量减少和反应定义方面存在差异。这些差异在医疗保健提供者中造成了困惑，他们正在纠结是否能够切实可行地提供一种双重护理体系——一种针对医疗保险患者，另一种针对非医疗保险患者——且该体系要有循证依据。通过本增刊，我们希望就政策与循证实践存在差异时与政策导向型医疗保健相关的问题和挑战对医疗保健提供者进行教育；提供关于实施NCD的指导；并强调药剂师在这一过程中的重要作用。
